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Article ; Online: Aromatase enzyme: Paving the way for exploring aromatization for cardio-renal protection.

Eissa, Manar A / Gohar, Eman Y

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 168, Page(s) 115832

Abstract: Documented male-female differences in the risk of cardiovascular and chronic kidney diseases have been largely attributed to estrogens. The cardiovascular and renal protective effects of estrogens are mediated via the activation of estrogen receptors ( ... ...

Abstract	Documented male-female differences in the risk of cardiovascular and chronic kidney diseases have been largely attributed to estrogens. The cardiovascular and renal protective effects of estrogens are mediated via the activation of estrogen receptors (ERα and ERβ) and G protein-coupled estrogen receptor, and involve interactions with the renin-angiotensin-aldosterone system. Aromatase, also called estrogen synthase, is a cytochrome P-450 enzyme that plays a pivotal role in the conversion of androgens into estrogens. Estrogens are biosynthesized in gonadal and extra-gonadal sites by the action of aromatase. Evidence suggests that aromatase inhibitors, which are used to treat high estrogen-related pathologies, are associated with the development of cardiovascular events. We review the potential role of aromatization in providing cardio-renal protection and highlight several meta-analysis studies on cardiovascular events associated with aromatase inhibitors. Overall, we present the potential of aromatase enzyme as a fundamental contributor to cardio-renal protection.
MeSH term(s)	Male ; Female ; Humans ; Aromatase ; Aromatase Inhibitors/pharmacology ; Androgens/pharmacology ; Estrogens/pharmacology ; Receptors, Estrogen ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/prevention & control
Chemical Substances	Aromatase (EC 1.14.14.1) ; Aromatase Inhibitors ; Androgens ; Estrogens ; Receptors, Estrogen
Language	English
Publishing date	2023-11-06
Publishing country	France
Document type	Meta-Analysis ; Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115832
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Article ; Online: G protein-coupled estrogen receptor 1 as a novel regulator of blood pressure.

Gohar, Eman Y

American journal of physiology. Renal physiology

2020 Volume 319, Issue 4, Page(s) F612–F617

Abstract: The mechanisms underlying hypertension are multifaceted and incompletely understood. New evidence suggests that G protein-coupled estrogen receptor 1 (GPER1) mediates protective actions within the cardiovascular and renal systems. This mini-review ... ...

Abstract	The mechanisms underlying hypertension are multifaceted and incompletely understood. New evidence suggests that G protein-coupled estrogen receptor 1 (GPER1) mediates protective actions within the cardiovascular and renal systems. This mini-review focuses on recent advancements in our understanding of the vascular, renal, and cardiac GPER1-mediated mechanisms that influence blood pressure regulation. We emphasize clinical and basic evidence that suggests GPER1 as a novel target to aid therapeutic strategies for hypertension. Furthermore, we discuss current controversies and challenges facing GPER1-related research.
MeSH term(s)	Animals ; Blood Pressure ; Cardiovascular System/metabolism ; Cardiovascular System/physiopathology ; Estradiol/metabolism ; Humans ; Hypertension/epidemiology ; Hypertension/metabolism ; Hypertension/physiopathology ; Kidney/metabolism ; Kidney/physiopathology ; Postmenopause/metabolism ; Receptors, Estrogen/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Risk Factors ; Sex Factors ; Signal Transduction
Chemical Substances	GPER1 protein, human ; Receptors, Estrogen ; Receptors, G-Protein-Coupled ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2020-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00045.2020
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Article: Editorial: Nuclear receptors in hemodynamics and blood pressure control.

Imig, John D / Wu, Jing / Gohar, Eman Y

Frontiers in physiology

2023 Volume 14, Page(s) 1290411

Language	English
Publishing date	2023-09-27
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1290411
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Article ; Online: Endothelin mediates sex-differences in acclimation to high salt diet in rats.

Nasci, Victoria L / Almutlaq, Rawan N / Pollock, David M / Gohar, Eman Y

Biology of sex differences

2023 Volume 14, Issue 1, Page(s) 70

Abstract: Introduction: Current understanding of sodium (Na: Methods: To test our hypothesis, male and female SD rats were implanted with telemeters and randomly assigned to treatment with A-182086, a dual ET: Results: We found that A-182086 increased blood ...

Abstract	Introduction: Current understanding of sodium (Na Methods: To test our hypothesis, male and female SD rats were implanted with telemeters and randomly assigned to treatment with A-182086, a dual ET Results: We found that A-182086 increased blood pressure in male and female SD rats fed either diet. Importantly, A-182086 eliminated sex-differences in natriuresis on NS and HS. In particular, A-182086 promotes HS-induced natriuresis in male rats rather than attenuating the natriuretic capacity of females. Further, the sex-difference in urinary ET-1 excretion in NS-fed rats was eliminated by A-182086. Conclusion: In conclusion, ET receptors are crucial for mediating sex-difference in the natriuretic capacity primarily through their actions in male rats.
MeSH term(s)	Rats ; Male ; Female ; Animals ; Sodium Chloride/pharmacology ; Sodium Chloride, Dietary/pharmacology ; Rats, Sprague-Dawley ; Receptor, Endothelin B/physiology ; Endothelins ; Sodium/metabolism ; Endothelin-1 ; Diet ; Acclimatization
Chemical Substances	Sodium Chloride (451W47IQ8X) ; Sodium Chloride, Dietary ; A 182086 ; Receptor, Endothelin B ; Endothelins ; Sodium (9NEZ333N27) ; Endothelin-1
Language	English
Publishing date	2023-10-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2587352-0
ISSN	2042-6410 ; 2042-6410
ISSN (online)	2042-6410
ISSN	2042-6410
DOI	10.1186/s13293-023-00555-2
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Article ; Online: Functional Interaction of Endothelin Receptors in Mediating Natriuresis Evoked by G Protein-Coupled Estrogen Receptor 1.

Gohar, Eman Y / Pollock, David M

The Journal of pharmacology and experimental therapeutics

2020 Volume 376, Issue 1, Page(s) 98–105

Abstract: The G protein-coupled estrogen receptor 1 (GPER1) mediates rapid estrogenic signaling. We recently reported that activation of GPER1 in the renal medulla evokes endothelin-1-dependent natriuresis in female, but not male, rats. However, the involvement of ...

Abstract	The G protein-coupled estrogen receptor 1 (GPER1) mediates rapid estrogenic signaling. We recently reported that activation of GPER1 in the renal medulla evokes endothelin-1-dependent natriuresis in female, but not male, rats. However, the involvement of the ET receptors, ET
MeSH term(s)	Animals ; Atrasentan/pharmacology ; Endothelin Receptor Antagonists/pharmacology ; Female ; Kidney Medulla/drug effects ; Kidney Medulla/metabolism ; Natriuresis ; Pyrrolidines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin A/metabolism ; Receptor, Endothelin B/metabolism ; Receptors, G-Protein-Coupled/agonists ; Receptors, G-Protein-Coupled/metabolism
Chemical Substances	A 192621 ; Endothelin Receptor Antagonists ; Gper1 protein, rat ; Pyrrolidines ; Receptor, Endothelin A ; Receptor, Endothelin B ; Receptors, G-Protein-Coupled ; Atrasentan (V6D7VK2215)
Language	English
Publishing date	2020-10-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.120.000322
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Article ; Online: Sex-Specific Contributions of Endothelin to Hypertension.

Gohar, Eman Y / Pollock, David M

Current hypertension reports

2018 Volume 20, Issue 7, Page(s) 58

Abstract: Purpose of review: Men and women differ in the prevalence, pathophysiology and control rate of hypertension in an age-dependent manner. The renal endothelin system plays a central role in sex differences in blood pressure regulation by control of sodium ...

Abstract	Purpose of review: Men and women differ in the prevalence, pathophysiology and control rate of hypertension in an age-dependent manner. The renal endothelin system plays a central role in sex differences in blood pressure regulation by control of sodium excretion and vascular function. Improving our understanding of the sex differences in the endothelin system, especially in regard to blood pressure regulation and sodium homeostasis, will fill a significant gap in our knowledge and may identify sex-specific therapeutic targets for management of hypertension. Recent findings: The current review will highlight evidence for the potential role for endothelin system in the pathophysiology of hypertension within three female populations: (i) postmenopausal women, (ii) women suffering from preeclampsia, or (iii) pulmonary arterial hypertension. Clinical trials that specifically address cardiovascular and renal diseases in females under different hormonal status are limited. Studies of the modulatory role of gonadal hormones and sex-specific mechanisms on critically important systems involved, such as endothelin, are needed to establish new clinical practice guidelines based on systematic evidence.
MeSH term(s)	Adult ; Age Factors ; Aged ; Blood Pressure/physiology ; Endothelin-1/physiology ; Female ; Homeostasis/physiology ; Humans ; Hypertension/physiopathology ; Kidney/physiopathology ; Male ; Middle Aged ; Postmenopause/physiology ; Pre-Eclampsia/physiopathology ; Pregnancy ; Risk Factors ; Sex Characteristics ; Sodium/blood
Chemical Substances	Endothelin-1 ; Sodium (9NEZ333N27)
Language	English
Publishing date	2018-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-018-0856-0
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Article ; Online: Sex differences in redox homeostasis in renal disease.

Mitchell, Tanecia / De Miguel, Carmen / Gohar, Eman Y

Redox biology

2020 Volume 31, Page(s) 101489

Abstract: Sex differences in redox signaling in the kidney present new challenges and opportunities for understanding the physiology and pathophysiology of the kidney. This review will focus on reactive oxygen species, immune-related signaling pathways and ... ...

Abstract	Sex differences in redox signaling in the kidney present new challenges and opportunities for understanding the physiology and pathophysiology of the kidney. This review will focus on reactive oxygen species, immune-related signaling pathways and endothelin-1 as potential mediators of sex-differences in redox homeostasis in the kidney. Additionally, this review will highlight male-female differences in redox signaling in several major cardiovascular and renal disorders namely acute kidney injury, diabetic nephropathy, kidney stone disease and salt-sensitive hypertension. Furthermore, we will discuss the contribution of redox signaling in the pathogenesis of postmenopausal hypertension and preeclampsia.
MeSH term(s)	Female ; Homeostasis ; Humans ; Kidney/metabolism ; Male ; Oxidation-Reduction ; Pregnancy ; Reactive Oxygen Species/metabolism ; Sex Characteristics
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2020-03-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2020.101489
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Article ; Online: Aromatase inhibition increases blood pressure and markers of renal injury in female rats.

Almutlaq, Rawan N / Newell-Fugate, Annie E / Evans, Louise C / Fatima, Huma / Gohar, Eman Y

American journal of physiology. Renal physiology

2022 Volume 323, Issue 3, Page(s) F349–F360

Abstract: Aromatase is a monooxygenase that catalyzes the rate-limiting step of estrogen biosynthesis from androgens. Aromatase inhibitors are widely used for the treatment of patients with hormone receptor-positive breast cancer. However, the effects of aromatase ...

Abstract	Aromatase is a monooxygenase that catalyzes the rate-limiting step of estrogen biosynthesis from androgens. Aromatase inhibitors are widely used for the treatment of patients with hormone receptor-positive breast cancer. However, the effects of aromatase inhibitors on cardiovascular and renal health in females are understudied. Given that estrogen is protective against cardiovascular and kidney diseases, we hypothesized that aromatase inhibition elevates blood pressure and induces kidney injury in female Sprague-Dawley rats. Twelve-week-old female rats were implanted with radiotelemetry transmitters to continuously monitor blood pressure. After baseline blood pressure recording, rats were randomly assigned to treatment with the aromatase inhibitor anastrozole (ASZ) or vehicle (Veh) in drinking water. Twenty days after treatment initiation, rats were shifted from a normal-salt (NS) diet to a high-salt (HS) diet for an additional 40 days. Rats were euthanized 60 days after treatment initiation. Body weight increased in both groups over the study period, but the increase was greater in the ASZ-treated group than in the Veh-treated group. Mean arterial pressure increased in ASZ-treated rats during the NS and HS diet phases but remained unchanged in Veh-treated rats. In addition, urinary excretion of albumin and kidney injury marker-1 and plasma urea were increased in response to aromatase inhibition. Furthermore, histological assessment revealed that ASZ treatment increased morphological evidence of renal tubular injury and proximal tubular brush border loss. In conclusion, chronic aromatase inhibition in vivo with ASZ increases blood pressure and markers of renal proximal tubular injury in female Sprague-Dawley rats, suggesting an important role for aromatization in the maintenance cardiovascular and renal health in females.
MeSH term(s)	Anastrozole/adverse effects ; Animals ; Aromatase Inhibitors/adverse effects ; Biomarkers ; Blood Pressure ; Estrogens ; Female ; Hypertension/chemically induced ; Kidney/pathology ; Neoplasms ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride, Dietary/adverse effects
Chemical Substances	Aromatase Inhibitors ; Biomarkers ; Estrogens ; Sodium Chloride, Dietary ; Anastrozole (2Z07MYW1AZ)
Language	English
Publishing date	2022-07-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00055.2022
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Article: G protein-coupled estrogen receptor 1 regulates renal endothelin-1 signaling system in a sex-specific manner.

Guthrie, Ginger L / Almutlaq, Rawan N / Sugahara, Sho / Butt, Maryam K / Brooks, Craig R / Pollock, David M / Gohar, Eman Y

Frontiers in physiology

2023 Volume 14, Page(s) 1086973

Abstract: Demographic studies reveal lower prevalence of hypertension among premenopausal females compared to age-matched males. The kidney plays a central role in the maintenance of sodium ( ... ...

Abstract	Demographic studies reveal lower prevalence of hypertension among premenopausal females compared to age-matched males. The kidney plays a central role in the maintenance of sodium (Na
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1086973
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Article ; Online: Emerging Roles for G Protein-Coupled Estrogen Receptor 1 in Cardio-Renal Health: Implications for Aging.

Singh, Ravneet / Nasci, Victoria L / Guthrie, Ginger / Ertuglu, Lale A / Butt, Maryam K / Kirabo, Annet / Gohar, Eman Y

Biomolecules

2022 Volume 12, Issue 3

Abstract: Cardiovascular (CV) and renal diseases are increasingly prevalent in the United States and globally. CV-related mortality is the leading cause of death in the United States, while renal-related mortality is the 8th. Despite advanced therapeutics, both ... ...

Abstract	Cardiovascular (CV) and renal diseases are increasingly prevalent in the United States and globally. CV-related mortality is the leading cause of death in the United States, while renal-related mortality is the 8th. Despite advanced therapeutics, both diseases persist, warranting continued exploration of disease mechanisms to develop novel therapeutics and advance clinical outcomes for cardio-renal health. CV and renal diseases increase with age, and there are sex differences evident in both the prevalence and progression of CV and renal disease. These age and sex differences seen in cardio-renal health implicate sex hormones as potentially important regulators to be studied. One such regulator is G protein-coupled estrogen receptor 1 (GPER1). GPER1 has been implicated in estrogen signaling and is expressed in a variety of tissues including the heart, vasculature, and kidney. GPER1 has been shown to be protective against CV and renal diseases in different experimental animal models. GPER1 actions involve multiple signaling pathways: interaction with aldosterone and endothelin-1 signaling, stimulation of the release of nitric oxide, and reduction in oxidative stress, inflammation, and immune infiltration. This review will discuss the current literature regarding GPER1 and cardio-renal health, particularly in the context of aging. Improving our understanding of GPER1-evoked mechanisms may reveal novel therapeutics aimed at improving cardio-renal health and clinical outcomes in the elderly.
MeSH term(s)	Aging ; Animals ; Estrogen Receptor alpha ; Estrogens ; Female ; GTP-Binding Proteins ; Kidney/metabolism ; Male ; Receptors, G-Protein-Coupled/metabolism
Chemical Substances	Estrogen Receptor alpha ; Estrogens ; Receptors, G-Protein-Coupled ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2022-03-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12030412
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